CCR5's Role in Cancer Metastasis
Research indicates that the CCR5 receptor is a potential “GPS” system of a cancer cell that promotes metastatic disease. Preclinical studies have shown that leronlimab blocks the calcium channel signaling of the CCR5 receptor and has the potential to disable the GPS system. CCR5 inhibition may disrupt signaling and ultimately the spread of CCR5 positive Circulating Tumor Cells (CTC’s). The majority of current therapies are directed to the primary tumor, rather than the movement or spread of cancer in the bloodstream. Metastatic disease, not the primary tumor, is the cause of death in the vast majority of cancer patients.
Key Properties of CCR5
The tumor microenvironment is the critical site where the battle against cancer is fought and won. During malignant cell transformation, the tumor microenvironment attracts cells that support tumor growth. The identification of the CCR5 receptor on the cell surface of tumor-associated macrophages (TAM’s) or M2 macrophages, regulatory T cells (T regs), and malignant cells in the tumor microenvironment is an important discovery in immuno-oncology. The M2 macrophage supports tumor progression, causes therapeutic resistance, stimulates proliferation, invasion, metastasis of tumor cells, and promotes angiogenesis (formation of blood supply to support tumor growth). We believe that CCR5 antagonism has the potential to knock out the M2 population and convert the M2 macrophage into an M1 macrophage (anti-tumor macrophage), which fights cancer rather than promotes tumor growth.
T regs play another critical role in the tumor microenvironment. T regs turn off the anti-tumor response. By blocking T regs, leronlimab has the potential to turn the anti-tumor response back on to leverage the immune systems' natural ability to fight cancer.
There is also an upregulation of the CCR5 receptor in malignant cell transformation, which enhances cellular invasion and endovascular migration. We believe there are many synergistic opportunities with leronlimab and traditional oncology treatments including chemotherapy, radiation, checkpoint inhibitors, CAR T immunotherapy, and PARP inhibitors in the fight against cancer.
Leronlimab and Cancer
On November 23, 2018, CytoDyn received FDA approval of its IND submission and was allowed to initiate a Phase 1b/2 clinical trial for metastatic triple-negative breast cancer (mTNBC) patients. On February 20, 2019, CytoDyn announced that leronlimab was able to reduce by more than 98% the incidence of human breast cancer metastasis in a mouse xenograft model for cancer through six weeks of administration with leronlimab (PRO 140). In May 2019, the U.S. Food and Drug Administration (FDA) granted Fast Track designation for leronlimab (PRO 140) for use in combination with carboplatin for the treatment of patients with CCR5-positive mTNBC. On February 21, 2020, CytoDyn announced Institutional Review Board approval to initiate a Phase 2 basket trial for 22 solid tumor cancers.
Useful Links
You can learn more about CCR5’s role in cancer and related research by viewing the videos and reading the articles below.
CCR5 Receptor Antagonists Block Metastasis to Bone of v-Src Oncogene-Transformed Metastatic Prostate Cancer Cell Lines
The CCL5/CCR5 Axis Promotes Metastasis in Basal Breast Cancer
CCR5 Governs DNA Damage Repair and Breast Cancer Stem Cell Expansion
Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer Patients
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